Studies will be initiated or continue to be directed toward the elucidation of humoral immune mechanisms potentially operative 1) in acquired experimental syphilis, and 2) following vaccination of rabbits with Treponema pallidum inactivated by time and Y-irradiation; methods for assessment will include passive protection, blockage of attachment, in vitro-in vivo neutralization, T. pallidum immobilization, and an in vitro radiolabeled staphyloccal protein A microassay. Studies will also be initiated or continue to be directed toward the elucidation of operative cell-mediated immune mechanisms; methods of assessment will include assays for in vitro phagocytosis and digestion of opsonized T. pallidum by macrophages (mPhi), in vitro destruction of T. pallidum by lymphokine-activated mPhi in the presence or absence of specific antibody, host-resistance to challenge following non-specific and specific in vivo mPhi activation by purified BCG cell wall skeletons, and in vitro destruction of T. pallidum by mPhi cationic protein 1. Functional and functional-related characteristics of murine monoclonal antibodies directed specifically against T. pallidum will be determined using several of these assay systems as a prelude to their use in collaborative studies designed to isolate putative "protective" immunogens and virulence factor(s) by affinity chromatography. Additionally, efforts will continue toward the development of an experimental congenital syphilis model in the rabbit and toward the characterization of innate humoral factor(s) which may influence pathogenesis and resistance in the neonatal rabbit. These studies should lead to 1) a more complete understanding of the role of the immune process during the pathogenesis of the disease; 2) methods for the assessment of the immune status of patients and potential future vaccinees; and 3) a sound rationale for the isolation of "protective" immunogens and virulence factors.